Outpatient cataract surgery: incident and procedural risk analysis do not support current clinical ophthalmology guidelines.

OBJECTIVE: To evaluate whether an ophthalmologist-led, non-anesthesia-supported, limited monitoring pathway for phacoemulsification/intraocular lens cataract surgery, can be performed safely with only a medical emergency team providing support. DESIGN: Retrospective, observational, cohort study. PARTICIPANTS: All patients who underwent elective phacoemulsification/intraocular lens surgery under topical anesthesia in the ophthalmology outpatient unit between January 1, 2011, and December 31, 2012. METHODS: Cataract surgery was performed by phacoemulsification under topical anesthesia. The intake process mainly embraced ophthalmic evaluation, obtaining a medical history, and proposing the procedure. A staff ophthalmologist performed the procedure assisted by 2 registered nurses in an independent outpatient clinic operating room within the hospital. The clinical pathway was without dedicated presence of or access to anesthesia service. Perioperative monitoring was limited to blood pressure and plethysmography preoperatively and intraoperatively. Patients were offered supportive care and instructed to avoid fasting and continue all their chronic medication. MAIN OUTCOME MEASURES: The primary outcome measure was the incidence of adverse events requiring medical emergency team (MET) interventions throughout the pathway. Secondary outcome measures were surgical ocular complication rates, use of oral sedatives, and reported reasons to perform the surgery in the classical operation room complex. RESULTS: Within the cataract pathway, 6961 cases (4347 patients) were eligible for analysis. Three MET interventions related to the phacoemulsification/intraocular lens pathway occurred in the 2-year study period, resulting in an intervention rate of 0.04%. None of the interventions was intraoperative. All 3 patients were diagnosed as vasovagal collapse and recuperated uneventfully. No hospital admittance was required. Eight other incidents occurred within the general ophthalmology outpatient unit population during the study period. CONCLUSIONS: Cataract surgery can be safely performed in an outpatient clinic, in the absence of the anesthesia service and with limited workup and monitoring. Basic first aid and basic life support skills seem to be sufficient in case of an adverse event. An MET provides a generous failsafe for this low-risk procedure.

No effect of the PPAR-gamma agonist rosiglitazone on ACTH or cortisol secretion in Nelson's syndrome and Cushing's disease in vitro and in vivo.

OBJECTIVE: Surgical tumor resection remains the primary treatment strategy in ACTH-secreting pituitary adenomas, i.e. Cushing's disease (CD) and Nelson's syndrome (NS). However, an effective long-term pharmacological regime is not available in patients with persistent ACTH-hypersecretion. The nuclear receptor peroxisome proliferator-activated receptor gamma (PPAR-gamma) is abundantly expressed in most pituitary adenomas. First encouraging data reported that the PPAR-gamma ligand rosiglitazone antagonizes ACTH hypersecretion and exerts also antiproliferative effects in pituitary cell lines. Herein, we studied the potential therapeutical effects of rosiglitazone in patients with ACTH-secreting pituitary adenomas in vitro and in vivo. MATERIALS AND METHODS: Seven patients with persistent ACTH-hypersecretion (3 with NS, 4 with persistent CD) were treated 5 months with rosiglitazone (4 - 16 mg/day). In vitro assays were performed in primary cell cultures obtained from eight additional patients with ACTH-secreting pituitary adenomas applying 80 microM rosiglitazone repeatedly over a time period of 14 days. RESULTS: Our long-term clinical trial with the PPAR-gamma activator rosiglitazone showed no amelioration of clinical symptoms nor an inhibiting effect on ACTH-secretion in vivo. In vitro, rosiglitazone treatment led to a statistically significant decrease of ACTH levels in 2 out of 8 primary cell cultures after 14 days compared to untreated controls. CONCLUSION: In contrast to the initially promising laboratory data gathered in pituitary cell line experiments and nude mice models, our experimental data obtained in primary human ACTH-expressing pituitary adenoma cell cultures as well as our clinical experience with a long-term rosiglitazone trial in approved antidiabetic doses support the recently reported disappointing reports on acute or short-term medical treatment of ACTH-hypersecretion with PPAR-gamma activators.

Specific accumulation of 18F-deoxyglucose in three-dimensional long-term cultures of human and rodent brain tissue.

AIM: Organotypic slice cultures (OSC) of human brain specimens represent an intriguing experimental model for translational studies addressing, e.g., stem cell transplantation in neurodegenerative diseases or targeting invasion by malignant glioma ex vivo. However, long-term viability and phenomena of structural reorganization of human OSC remain to be further characterized. Here, we report the use of (18)F-deoxyglucose (FDG) for evaluating the viability of brain slice preparations obtained either from postnatal rats or human hippocampal specimens. METHODS: Anatomically well preserved human hippocampi obtained from epilepsy surgery and rat hippocampus slice cultures obtained from six day old Wistar rats were dissected into horizontal slices. The slices were incubated with FDG in phosphate buffered saline up to 1 h, either with or without supplementation of glucose at a concentration of 2.5 mg/ml. Radioactivity within the medium or slice cultures was measured using a gamma-counter. In addition, distribution of radioactivity was autoradiographically visualized and quantified as counts per mm(2). RESULTS: In rat hippocampal slices, FDG accumulated with 1 300 000 +/- 68 000 counts/mm(2), whereas the incorporation of the radioactive label in human slices was in the order of 1 500 000 +/- 370 000 counts/mm(2). The elevation of glucose concentration within the medium led to a significant three-fold decrease of FDG accumulation in rat slices and to a 2.4-fold decrease in human specimens. CONCLUSIONS: FDG accumulated in organotypic brain cultures of human or rodent origin. FDG is thus suited to investigate the viability of OSC. Furthermore, these preparations open new ways to study the factors governing cerebral FDG uptake in brain tissue ex vivo.

Monosynaptic projections from the nucleus tractus solitarii to C1 adrenergic neurons in the rostral ventrolateral medulla: comparison with input from the caudal ventrolateral medulla.

The rostral ventrolateral medulla (RVL) contains reticulospinal adrenergic (C1) neurons that are thought to be sympathoexcitatory and that form the medullary efferent limb of the baroreceptor reflex pathway. The RVL receives direct projections from two important autonomic regions, the caudal ventrolateral medulla (CVL) and the nucleus tractus solitarii with immunocytochemical identification of C1 adrenergic neurons in the RVL to compare the morphology of afferent input from these two autonomic regions into the RVL. NTS (n = 203) and CVL (n = 380) efferent terminals had similar morphology and vesicular content, but CVL efferent terminals were slightly larger than NTS efferent terminals. Overall, efferent terminals from either region were equally likely to contact adrenergic neurons in the RVL (21% for NTS, 25% for CVL). Although efferents from both regions formed both symmetric and asymmetric synapses, NTS efferent terminals were statistically more likely to form asymmetric synapses than CVL efferent terminals. CVL efferent terminals were more likely to contact adrenergic somata than were NTS efferents, which usually contacted dendrites. These findings 1) support the hypothesis that a portion of NTS efferents to the RVL may be involved in sympathoexcitatory, e.g., chemoreceptor, reflexes (via asymmetric synapses), whereas those from the CVL mediate sympathoinhibition (via symmetric synapses); and 2) provide an anatomical substrate for differential postsynaptic modulation of C1 neurons by projections from the NTS and CVL. With their more frequent somatic localization, CVL inhibitory inputs may be more influential than excitatory NTS inputs in determining the discharge of RVL neurons.

Neurons in the barosensory area of the caudal ventrolateral medulla project monosynaptically on to sympathoexcitatory bulbospinal neurons in the rostral ventrolateral medulla.

Neurons in the caudal ventrolateral medulla may function as interneurons in the baroreceptor reflex are by inhibiting sympathoexcitatory bulbospinal neurons in rostral ventrolateral medulla. While some caudal ventrolateral medullary neurons are excited orthodromically by baroreceptors and antidromically from the rostral ventrolateral medulla, there is no anatomical evidence to prove that these barosensory neurons of the caudal ventrolateral medulla monosynaptically innervate the bulbospinal neurons in the rostral ventrolateral medulla. To establish the presence of such a direct projection, barosensory neurons were identified in the rostral caudal ventrolateral medulla of anesthetized rats by criteria that they spontaneously discharged with a cardiac rhythm and were excited by baroreceptor stimulation. The anterograde tracer biocytin was iontophoresed onto these neurons and, in the same animal, the retrograde tracer wheatgerm-agglutinated apo-horseradish peroxidase conjugated to gold particles was injected by micropressure into the ipsilateral spinal (thoracic level 3) intermediolateral cell column to label bulbospinal neurons. After 18-24 h, rats were killed and sections through the rostral ventrolateral medulla were processed for both markers. By light microscopy, numerous biocytin-labeled varicose processes overlapped rostral ventrolateral medullary neurons containing wheatgerm-agglutinated apo-horseradish peroxidase conjugated to gold particles. By electron microscopy, biocytin was found in axons and terminals. The terminals (n = 76) were large (0.6-1.2 microns in diameter), contained numerous small, clear vesicles and formed primarily symmetric synapses on perikarya and large (1.5-4.5 microns) dendrites within the rostral ventrolateral medulla. Some of these target neurons contained wheatgerm-agglutinated apo-horseradish peroxidase conjugated to gold particles associated with lysosomes and multivesicular bodies in the cytoplasm. The results indicate that: (i) neurons in the barosensory sympathoinhibitory region of the caudal ventrolateral medulla directly synapse on bulbospinal neurons in the rostral ventrolateral medulla; and (ii) the synaptic profile (symmetric synapse) and location (perikarya and large dendrites) is consistent with the conclusion that baroreceptor neurons of the caudal ventrolateral medulla potently and monosynaptically inhibit sympathoexcitatory neurons of the rostral ventrolateral medulla. The findings support the hypothesis that the barosensory region of the rostral caudal ventrolateral medulla is an intermediate relay in the baroreceptor reflex are.

Identification of baroreceptor reflex interneurons in the caudal ventrolateral medulla.

Interrupting neuronal activity in the caudal ventrolateral medulla (CVL) abolishes baroreceptor-mediated sympathoinhibition and vasodepressor responses. In the present study we identified CVL neurons that function as interneurons in the baroreceptor reflex arc. The mean antidromic onset latency of CVL neurons (5 ms) after stimulation in the rostral ventrolateral medulla (RVL) suggests that they transmit information to the RVL via unmyelinated axons. Stimulation of baroreceptor afferents in the aortic depressor nerve (ADN) excited CVL neurons projecting to the RVL with onset latencies between 15 and 45 ms. The short-latency ADN stimulus-evoked excitation of CVL barosensory interneurons preceded the onset of the ADN stimulus-evoked inhibition of RVL-spinal sympathoexcitatory neurons. Longer-latency ADN-evoked CVL neuronal responses may arise from activation of unmyelinated ADN afferents that can prolong the inhibition of RVL sympathoexcitatory neurons. The excitation of CVL barosensory interneurons resulting from the systolic pressure rise was followed by a period of decreased excitability of RVL sympatho-excitatory neurons, which was of comparable duration to the increase in the discharge probability of CVL neurons. Our characterization of baroreceptor reflex interneurons in the CVL suggests that transmission of baroreceptor information involves a complex activation of medullary interneurons responding selectively to different aspects of the arterial pressure stimulus.

Quantitative analysis of bulbospinal projections from the rostral ventrolateral medulla: contribution of C1-adrenergic and nonadrenergic neurons.

The contribution of C1-adrenergic and nonadrenergic neurons to the spinal projection from the rostral ventrolateral medulla (RVLM) and their relative innervation density throughout thoracic spinal segments were examined by combining the Fluorogold (FG) retrograde tracing technique with immunofluorescent labeling for the epinephrine-synthesis enzyme phenylethanolamine N-methyltransferase (PNMT). The results indicate that the RVLM-spinal projection is comprised of both PNMT-positive and PNMT-negative neurons located in the subretrofacial area of the RVLM, approximately 1 to 1.7 mm rostral to obex. The bulbospinal projection from the RVLM is predominantly ipsilateral, and bulbospinal neurons do not appear to be organized within the RVLM in a manner indicating their segmental termination site. Eighty-one percent (+/- 4%, n = 2) of the PNMT-positive cells in the ipsilateral subretrofacial RVLM were retrogradely labeled after unilateral FG injections into multiple thoracic levels of the intermediolateral cell column (IML). Following single level FG injections, the number of retrogradely labeled PNMT-positive neurons in the subretrofacial RVLM decreased with injections in more caudal thoracic segments, indicating a heavier innervation of the upper thoracic IML by C1 neurons. PNMT-negative neurons were the main component of the RVLM-spinal population with 63 +/- 8% (n = 7) of the non-PNMT-containing neurons within the ipsilateral subretrofacial RVLM innervating all thoracic levels of the IML. The results indicate that both C1-adrenergic and nonadrenergic neurons in the RVLM make a substantial contribution to the innervation of the IML.

Cyanide excites medullary sympathoexcitatory neurons in rats.

Microinjections of cyanide (300 pmol) into the cardiovascular portion of the rostral ventrolateral reticular nucleus (RVL) of anesthetized rats (paralyzed and ventilated) produced a pressor response (26.5 +/- 1.6 mmHg, n = 7) and a transient depression of phrenic nerve discharge (90 +/- 8%, n = 5). Microiontophoretic applications of cyanide (less than or equal to 100 nA, 5-40 s) excited the RVL-spinal sympathoexcitatory neurons (31 out of 31). The response was dose dependent, reversible, independent of the baroreflex input to these neurons, and different from the responses of units with spontaneous discharge synchronized with the lung inflation or with unidentified function. The cyanide-induced excitation of the RVL-spinal sympathoexcitatory neurons was reversibly abolished by CO2+, applied iontophoretically at a dose at which the baroreflex inhibition of these neurons was not markedly affected whereas iontophoretic applications of kynurenic acid, a glutamate receptor antagonist, did not alter the response of the RVL-spinal sympathoexcitatory neurons to cyanide. It was concluded that cyanide induces a rapid Ca(2+)-dependent response of the RVL-spinal sympathoexcitatory neurons, which may underlie the cellular mechanism of these neurons in responding to ischemia-hypoxia.

Cardiorespiratory effects of DL-homocysteic acid in caudal ventrolateral medulla.

We carried out experiments in urethan-anesthetized rats to determine 1) whether increasing the activity of small groups of neurons in the caudal ventrolateral medulla (CVLM) by injecting picomoles of an excitatory amino acid altered cardiovascular and/or respiratory homeostasis and 2) whether the depressor responses after chemical excitation in the CVLM were elicited only from the immunohistochemically identified catecholamine-containing cell group. In discrete sites in the CVLM, unilateral injections of 1-12 nl (20-240 pmol) of DL-homocysteic acid (DLH; 20 mM, pH 7.4) selectively or concomitantly inhibited arterial pressure, heart rate, and diaphragm electromyogram (EMG) activity. In the region in which chemical excitation slowed breathing, units were recorded extracellularly that discharged with respiratory periodicity. Sites where the smallest volumes of DLH decreased arterial pressure were located outside the immunohistochemically identified DBH-positive cell bodies. These data suggest that either the same or neighboring neurons in the CVLM are involved in the central neural circuitry for both cardiovascular and respiratory control and that cells other than the catecholaminergic cell group are important in medullary depressor responses.